Abstract

Introduction: It is currently recognized that glycerinergic transmission is critical for neuronal inhibition within the nucleus accumbens (nAc). The glycine receptor (GlyR) is a ligand-gated chloride channel composed of three alpha subunits (α1-α3) and two beta (β) subunits. GlyR subunit composition determines its function, subcellular localization, and pharmacological properties. It is widely accepted that GlyR subunit composition changes during developmental stages. However, variations in GlyR subunit expression during aging have not been investigated yet. In this work, we used a combination of molecular and electrophysiological techniques to assess whether glycerinergic transmission in the nAc changes with age, which could explain the motor and/or cognitive disorders frequently found with aging. Materials and methods: We performed western blot, qPCR and immunohistochemistry (IHC), as well as electrophysiological recordings in the nAc of adolescent (1-1.5 mo), adult (3-6 mo), and aged C57BL/6J mice (12-14 mo). Results: Immunostaining experiments using a specific antibody to detect all GlyR α subunits showed that the subcellular localization of these receptors was altered. q-PCR analysis indicated that the alpha 1subunit, and to a lesser extent the alpha 2 subunit, was increased in aged mice. In addition, western blot experiments demonstrated that β subunit levels were decreased in aged mice. Finally, electrophysiological studies showed that glycinergic activity was significantly decreased in neurons from nAc in aged mice. Discussion: Using a combination of proteomic and electrophysiological studies, we demonstrated that glycine transmission in the nAc is modified in aging.